Jorge S. López Camelo

Linking childhood poverty and cognition: environmental mediators of non-verbal executive control in an Argentine sample.

Tests of attentional control, working memory, and planning were administered to compare the non-verbal executive control performance of healthy children from different socioeconomic backgrounds. In addition, mediations of several sociodemographic variables, identified in the literature as part of the experience of child poverty, between socioeconomic status and cognitive performance were assessed. Results show: (1) significant differences in performance between groups in most dependent variables analyzed - however, not in all variables associated with attentional control domains; (2) significant indirect effects of literacy activities on working memory and fluid processing domains, as well as computer resources effects on fluid processing; and (3) marginal indirect effects of computer resources on attentional control and working memory domains. These findings extend analysis of the impact of poverty on the development of executive control, through information based on the assessment of combined neurocognitive paradigms and the identification of specific environmental mediators.

Software for Y-haplogroup predictions: a word of caution

The development of online software designed for genetic studies has been exponentially growing, providing numerous benefits to the scientific community. However, they should be used with care, since some require adjustments. The efficiency of two programs for haplogroup prediction was tested with 119 samples of known haplotypes and haplogroups from Argentine populations. Quantitative estimates of the predictive quality of both software systems were computed with the uncertainty coefficient; and sensitivity, specificity, positive, and negative likelihood ratios were also calculated to assert the reliability of both programs, showing high probabilities of assigning an incorrect haplogroup.

Prevalencia al nacimiento de 27 anomalías congénitas seleccionadas, en 7 regiones geográficas de la Argentina

OBJECTIVEnThe aim of the present work was to estimate the frequency of 27 birth defects in 7 geographical regions of Argentina.nnnMATERIAL AND METHODSnObservational, cross-sectional, descriptive design. A sample of 21,844 new born with birth defects was selected, ascertained from 855,220 births, between 1994 and 2007, in 59 hospitals belonging to the ECLAMC network. In order to identify regions of high frequency a Poisson regression was used, adjusted by different hospitals from the same region. The model included a time variable to detect secular trends and 6 dummy variables for 7 predefined geographical regions: Metropolitana (MET); Pampa (PAM); Centro (CEN); Cuyo (CUY); Noroeste (NOA); Nordeste (NEA) and Patagonia (PAT).nnnRESULTSnHigh frequencies regional analysis showed the following significant results: PAM: severe hypospadias; CEN: spina bifida, microtia, cleft lip with cleft palate, polycystic kidney, postaxial polydactyly and Down syndrome; CUY: postaxial polydactyly; NOA: omphalocele, gastroschisis, cleft lip without cleft palate, cleft lip with cleft palate, anorectal atresia/stenosis, indeterminate sex, preaxial polydactyly and pectoral agenesis; PAT: cleft lip without cleft palate.nnnCONCLUSIONnOut of the 27 congenital anomalies analyzed, fourteen showed a frequency significatively higher in one or more regions.

Economic activity and congenital anomalies: an ecologic study in Argentina.

Se analiza la asociacion entre la actividad industrial y 34 anomalias congenitas en la Argentina durante 1982 y 1994, analizando un total de 614.700 nacimientos. Entre las correlaciones significativas se identifico asociacion entre la industria textil y la anencefalia, y la fabricacion de motores y turbinas y la microcefalia. Estos resultados son concordantes con otros estudios de salud ocupacional. El articulo contiene tablas estadisticas de las anomalias congenitas estudiadas, el numero de casos, y las asociaciones entre estas y la actividad industrial

A comparative analysis of prenatal care and fetal growth in eight South American countries.

There has been little work that comprehensively compared the relationship between prenatal care and infant health across multiple countries using similar data sources and analytical models. Such comparative analyses are useful for understanding the background of differences in infant health between populations. We evaluated the association between prenatal care visits and fetal growth measured by birth weight (BW) in grams or low birth weight (<2500 grams; LBW) adjusted for gestational age in eight South American countries using similarly collected data across countries and the same analytical models. OLS and logistic regressions were estimated adjusting for a large set of relevant infant, maternal, and household characteristics and birth year and hospital fixed effects. Birth data were acquired from 140 hospitals that are part of the Latin American Collaborative Study of Congenital Malformations (ECLAMC) network. The analytical sample included 56,014 live-born infants (∼69% of total sample) with complete data born without congenital anomalies in the years 1996–2011 in Brazil, Argentina, Chile, Venezuela, Ecuador, Colombia, Bolivia, and Uruguay. Prenatal care visits were significantly (at p<.05) and positively associated with BW and negatively associated with LBW for all countries. The OLS coefficients ranged from 9 grams per visit in Bolivia to 36 grams in Uruguay. The association with LBW was strongest for Chile (ORu200a=u200a0.87 per visit) and lowest for Argentina and Venezuela (ORu200a=u200a0.95). The association decreased in the recent decade compared to earlier years. Our findings suggest that estimates of association between prenatal care and fetal growth are population-specific and may not be generalizable to other populations. Furthermore, as one of the indicators for a country’s healthcare system for maternal and child health, prenatal care is a highly variable indicator between countries in South America.

Random inbreeding, isonymy, and population isolates in Argentina

Population isolates are an important tool in identifying and mapping genes of Mendelian diseases and complex traits. The geographical identification of isolates represents a priority from a genetic and health care standpoint. The purpose of this study is to analyze the spatial distribution of consanguinity by random isonymy (FST) in Argentina and its relationship with the isolates previously identified in the country. FST was estimated from the surname distribution of 22.6 million electors registered for the year 2001 in the 24 provinces, 5 geographical regions, and 510 departments of the country. Statistically significant spatial clustering of FST was determined using the SaTScan V5.1 software. FST exhibited a marked regional and departamental variation, showing the highest values towards the North and West of Argentina. The clusters of high consanguinity by random isonymy followed the same distribution. Recognized Argentinean genetic isolates are mainly localized at the north of the country, in clusters of high inbreeding. Given the availability of listings of surnames in high-capacity storage devices for different countries, estimating FST from them can provide information on inbreeding for all levels of administrative subdivisions, to be used as a demographic variable for the identification of isolates within the country for public health purposes.

About the letter “Comments on the article, “Software for Y-Haplogroup Predictions, a Word of Caution”

Dear Sirs: The letter by Dr. Athey entitled “Comments on the article, “Software for Y-Haplogroup Predictions, a Word of Caution” discusses a paper of our authoring in the present Journal [1]. Though at first glance his opinion may seem reasonable, a careful analysis reveals a series of mistakes committed by Dr. Athey. In the mentioned letter, one of the main concerns of Dr. Athey is the amount of short tandem repeats (STRs) that were analyzed. He comments that seven markers should be avoided, explaining that an increase of that amount augments the probability of assignment, stating that “With the addition of a sufficient number of markers, the prediction probability for the correct haplogroup can be ‘driven’ past 99% in nearly all cases, and this almost always occurs by the point where 20 markers have been used.” Nonetheless, he does not make reference to any sort of validation study, so said 99% must only refer to the probability of assignment his own software provides. What is more, Dr. Athey seems oblivious that our paper examined this software’s predictive values in different cutoff points, up to 95% of probability of assignment, still obtaining inadequate predictive values on said cutoff point. Twelve of our haplotypes proposed from 100% to 99.6% probability of assignment to the R1b haplogroup in the Haplogroup Predictor, while none of those samples belong to the said haplogroup. In the R haplogroup, one haplotype gives 99.8% probability to an erred haplogroup (E1b1b), while 14 give from 100% to 99.4%, assigning these samples to the R1b haplogroup, and were considered as correct predictions. Note that in these cases, the predicted haplogroup follows the nomenclature of the software, and the probability was not pooled by major branches. If the seven markers of the minimal haplotype were not a proper set, Dr. Athey’s software should not provide such high probabilities of assignment in these cases, since it misleads the user. Unfortunately, Dr. Athey’s mention that seven Y-STRs are too few occurs only in his letter; neither of the two papers of his authoring [2, 3] available at the Haplogroup Predictor’s website (http:// www.hprg.com/hapest5/) nor the software instructions (http://www.hprg.com/hapest5/page4.html) explain that the user should employ more than seven markers. Otherwise, we would not have attempted to use it. Moreover, a simple glance at recent literature where the Haplogroup Predictor was employed clearly shows that researchers do not use such high amounts of Y-STRs when they rely on the Haplogroup Predictor; for instance, Salas et al. [4] used the seven Y-STRs we did, plus DYS 385 and Petrejcikova et al. [5] only 12 Y-STRs. His statement “...indeed, the seven-marker dataset apparently resulted from a study carried out over five M. Muzzio :V. Ramallo : J. M. B. Motti :M. R. Santos : J. S. Lopez Camelo :G. Bailliet Laboratorio de Genetica Molecular Poblacional, Instituto Multidisciplinario de Biologia Celular (IMBICE), CICPBA, CCT, La Plata–CONICET, La Plata, Argentina

Asociación entre polimorfismos del gen NAT2 y fisura labiopalatina no sindrómica en Argentina

Background: NAT genes are considered candidate genes for the genetic predisposition to non-syndromic Cleft lip with or without cleft palate (NSCLP), since they codify for N-acetyltransferases, enzymes responsible for the biotransformation of arylamines, hydrazine drugs, and a great number of toxins and carcinogens present in diet, cigarette smoke, and environment. Aim: To determine the association between alleles determining slow acetylator phenotype and the risk of NSCLP. Material and methods: We analyzed *5 (481C>T), *6 (590G>A) and *7 (857G>A) alleles which determine the slow acetylator phenotype and *4 (wild type) allele by polymerase chain reaction/restriction fragment length polymorphism in 97 progenitor-case trios of NSCLP in Argentinian Obstetric Wards. We evaluated the transmission disequilibrium (TDT). Results: TDT showed a positive association between allele *5 and NSCLP (odds ratio=1.6; p=0.03). Conclusions: The presence of *5 allele is significantly higher in cases with congenital NSCLP.BACKGROUNDnNAT genes are considered candidate genes for the genetic predisposition to non-syndromic Cleft lip with or without cleft palate (NSCLP), since they codify for N-acetyltransferases, enzymes responsible for the biotransformation of arylamines, hydrazine drugs, and a great number of toxins and carcinogens present in diet, cigarette smoke, and environment.nnnAIMnTo determine the association between alleles determining slow acetylator phenotype and the risk of NSCLP.nnnMATERIAL AND METHODSnWe analyzed *5 (481C>T), *6 (590G>A) and *7 (857G>A) alleles which determine the slow acetylator phenotype and *4 (wild type) allele by polymerase chain reaction/restriction fragment length polymorphism in 97 progenitor-case trios of NSCLP in Argentinian Obstetric Wards. We evaluated the transmission disequilibrium (TDT).nnnRESULTSnTDT showed a positive association between allele *5 and NSCLP (odds ratio = 1,6; p = 0,03).nnnCONCLUSIONSnThe presence of *5 allele is significantly higher in cases with congenital NSCLP.

Methodological approaches to evaluate teratogenic risk using birth defect registries: advantages and disadvantages

Background Different approaches have been used in case-control studies to estimate maternal exposure to medications and the risk of birth defects. However, the performance of these approaches and how they affect the odds ratio (OR) estimates have not been evaluated using birth-defect surveillance programmes. The aim of this study was to evaluate the scope and limitations of three case-control approaches to assess the teratogenic risk of birth defects in mothers exposed to antiepileptic medications, insulin, or acetaminophen. Methodology/Principal Findings We studied 110,814 non-malformed newborns and 58,514 live newborns with birth defects registered by the Latin American Collaborative Study of Congenital Anomalies (ECLAMC) between 1967 and 2008. Four controls were randomly selected for each case in the same hospital and period, and three different control groups were used: non-malformed newborns (HEALTHY), malformed newborns (SICK), and a subgroup of SICK, only-exposed cases (OECA). Associations were evaluated using OR and Pearsons chi-square (P<0.01). There were no concordance correlations between the HEALTHY and OECA designs, and the average OR differences ranged from 3.0 to 11.5 for the three evaluated medicines. The overestimations observed for HEALTHY design were increased as higher OR values were given, with a high and statistically significant correlation between the difference and the mean. On the contrary, the concordance correlations obtained between the SICK and OECA designs were quite good, with no significant differences in the average risks. Conclusions The HEALTHY design estimates the true population OR, but shows a high rate of false-positive results presumably caused by differential misclassification bias. This bias decreases with the increase of the proportion of exposed controls. SICK and OECA odds ratios cannot be considered a direct estimate of the true population OR except under certain conditions. However, the SICK and OECA designs could provide practical information to generate hypotheses about potential teratogens.

Biosocial correlates and spatial distribution of consanguinity in South America.

To analyze potential biosocial factors in consanguineous unions according to the level of consanguinity and its spatial distribution in South America.